A model of left ventricular function in the denervated heart

A model has been formulated for the function of the denervated left ventricle. Using the model it is possible to generate realistic waveforms for aortic flow, aortic pressure, left ventricular volume and left ventricular pressure over a wide range of simulated haemodynamic conditions. The effect of changes in contractile state is introduced through the concept of left ventricular pumping capacity. Model results compare well with similar data obtained from denervated hearts in open-chest dogs anaesthetized with halothane under positive pressure ventilation. Simulation of changes in contractile state shows excellent agreement with data published by previous investigators.     

Mesenchymal stem cells from ischemic heart disease patients improve left ventricular function after acute myocardial infarction

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immune-compromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x 10(5) cells in 20 microl, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 +/- 2% vs. 36 +/- 2%; P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 +/- 3% vs. 16 +/- 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 +/- 0.3% of injected cells) expressed von Willebrand factor (16.9 +/- 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning.     

Computational modeling of left heart diastolic function: examination of ventricular dysfunction

A computational model that accounts for blood-tissue interaction under physiological flow conditions was developed and applied to a thin-walled model of the left heart. This model consisted of the left ventricle, left atrium, and pulmonary vein flow. The input functions for the model included the pulmonary vein driving pressure and time-dependent relationship for changes in chamber tissue properties during the simulation. The Immersed Boundary Method was used for the interaction of the tissue and blood in response to fluid forces and changes in tissue pathophysiology, and the fluid mass and momentum conservation equations were solved using Patankar's Semi-Implicit Method for Pressure Linked Equations (SIMPLE). This model was used to examine the flow fields in the left heart under abnormal diastolic conditions of delayed ventricular relaxation, delayed ventricular relaxation with increased ventricular stiffness, and delayed ventricular relaxation with an increased atrial contraction. The results obtained from the left heart model were compared to clinically observed diastolic flow conditions, and to the results from simulations of normal diastolic function in this model [1]. Cases involving impairment of diastolic function were modeled with changes to the input functions for fiber relaxation/contraction of the chambers. The three cases of diastolic dysfunction investigated agreed with the changes in diastolic flow fields seen clinically. The effect of delayed relaxation was to decrease the early filling magnitude, and this decrease was larger when the stiffness of the ventricle was increased. Also, increasing the contraction of the atrium during atrial systole resulted in a higher late filling velocity and atrial pressure. The results show that dysfunction can be modeled by changing the relationships for fiber resting-length and/or stiffness. This provides confidence in future modeling of disease, especially changes to chamber properties to examine the effect of local dysfunction on global flow fields.     

应用Tei指数评价高血压心脏病患者左心室整体功能的研究

目的:探讨超声对高血压心脏病患者左心室整体功能评价的临床价值.方法:69例高血压心脏病患者分为3组:A组26例左室壁厚度正常,B组23例仅室间隔增厚,C组20例室间隔与左室后壁均增厚,同时选择正常健康者D组48人为对照.常规行超声心动图检查,测量并计算出二尖瓣口血流频谱舒张早期和舒张晚期血流峰值之比(E/A)、左室射血分数(LVEF)及Tei指数等评价参数.结果:高血压心脏病A、B组LVEF值均在正常范围,C组LVEF值有所下降,但与对照组比较差异均无统计学意义(P>0.05),但E/A值均较对照组减小(P<0.05);高血压心脏病A、B和C组Tei指数分别为(0.49±0.15)、(0.56±0.10)和(0.56±0.10),高于正常对照组的(0.32±0.08)(P<0.05).结论:在LVEF正常情况下Tei指数能更早地全面反映高血压心脏病患者左心功能下降情况,并且不受心率、心室几何形态,心室收缩和舒张压等因素的影响,为临床早期干预治疗防止心衰发生提供了依据.     

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.     

Interaction between glucose utilization and left ventricular heart function in type I-diabetics

The aim of the present study was to check whether equal, therapeutically relevant, positively inotropic doses of different adrenergic agents elicit equal inotropic and metabolic effects in 6 type I-diabetics as in 6 matched nondiabetic subjects. The effects of increasing doses of norepinephrine (NE)- and orciprenaline (0.12, 0.20, 0.33 microgram/kg min) on heart function (systolic time interval, heart rate, blood pressure) and on serum fatty acid (NEFA), glucose, lactate, pyruvate and insulin concentrations were recorded. In the therapeutic dose range, NE, and orciprenaline elicited in diabetics without clinical signs of any cardiovascular disease a diminished myocardial inotropic response (20-40%), less marked vascular effects (vasoconstriction, vasodilatation), but greater metabolic changes in right atrial blood (NEFA, pyruvate, lactate) compared to matched controls (p less than 0.05). The smaller increase of cardiac performance in diabetics to exogenous catecholamines cannot be explained by sympathetic cardiac denervation, since chronotropic beta 1-beta 2-stimulation with orciprenaline provoked nearly equal dose-dependent changes in diabetics and controls. It is suggested that the smaller positive inotropic effect during NE and orciprenaline infusion in type I-diabetics is a result first of all of alterations in myocardial energy turnover in diabetes due to reduced myocardial glucose utilization. It seems necessary to secure continuous myocardial glucose utilization and subnormal NEFA concentrations in the serum during the therapeutic application of inotropic adrenergic agents in severe cardiac failure and cardiogenic shock in diabetics.     

Characterization of the phospholemman knockout mouse heart: depressed left ventricular function with increased Na-K-ATPase activity

Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis that PLM is part of the cardiac Na-K pump complex and provides the link between kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca exchanger activity and may be involved in cell volume regulation. This study characterized the phenotype of the PLM knockout (KO) mouse heart to further our understanding of PLM function in the heart. PLM KO mice were bred on a congenic C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly depressed cardiac contractile function in PLM KO mice, which was exacerbated when hearts were isolated and Langendorff perfused. There were no significant differences in action potential morphology in paced Langendorff-perfused hearts. Depressed contractile function was associated with a mild cardiac hypertrophy in PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild-type controls. SDS-PAGE and Western blot analysis of ventricular homogenates revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal changes in ventricular protein expression, indicating that deletion of PLM was the primary reason for the observed PLM KO phenotype. These studies demonstrate that PLM plays an important role in the contractile function of the normoxic mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K-ATPase activity, indirectly affecting intracellular Ca and hence contractile function.     

Granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases left ventricular function. An echocardiographic study in cancer patients

To study the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the heart, echocardiographic assessments of left ventricular (LV) end-diastolic and end-systolic (ES) diameters (D), ejection fraction (EF) and cardiac output (CO) were done in six male patients (28-70 years of age) with advanced sarcoma (Group 1), prior to (day -1-0), during (day 7-9) and after (day 20-21) a first course of i.v. doxorubicin (day 0) without GM-CSF and a second course (3 weeks after the first one) with GM-CSF 250 microg/m(2)subcutaneously and daily from day 1-11. A similar study was done in ten female patients with advanced breast cancer (31-58 years of age, Group 2) for a first course of doxorubicin+cyclophosphamide with GM-CSF (same schedule as in Group 1). As compared to the mean of values prior to and after the course with GM-CSF in Group 1 and 2, the LVESD during GM-CSF administration transiently increased by median 6% (range -19 to 30%, P<0.05) vs -9% (-21 to 6%, not significant) in the first course without GM-CSF in Group 1 (P<0.05 between courses). The CO and EF tended to decrease during GM-CSF. GM-CSF thus causes a small and transient decrease of LV contractility.     

Efficacy and safety of atrial fibrillation ablation in heart failure patients with left ventricular ejection fraction less than 50%

IntroductionThe efficacy of catheter ablation in patients with low cardiac function has been previously reported; however, only a few studies have included mid-range ejection fraction (mrEF). This study aimed to evaluate the efficacy and safety of atrial fibrillation (AF) ablation in patients with left ventricular ejection fraction (LVEF) < 50%.MethodsThis study retrospectively analyzed 79 patients (reduced ejection fraction [rEF]/mrEF, 38/41; paroxysmal/persistent, 37/42; heart failure hospitalizations within one year before ablation, 36 [45.6%]) who underwent the first ablation procedure at our hospital from April 2017 to December 2021. Radiofrequency ablation and cryoablation were performed for 69 and 10 patients, respectively.ResultsComplications included pacemaker implantation for postoperative sick sinus syndrome in one patient and inguinal hematoma in one patient. Regarding efficacy, there were significant postoperative improvements in echocardiographic data, blood test values, and diuretic use. After a mean follow-up of 60 months, 86.1% patients had no AF recurrence. There were 9 heart failure hospitalizations (11.4%) and 5 all-cause deaths (6.3%); no significant differences were found between the rEF and mrEF groups. No significant predictors of AF recurrence were found in preoperative patient characteristics.ConclusionAF ablation in patients with LVEF <50% significantly improved cardiac and renal functions with few complications, resulting in a high non-recurrence rate and reduced heart failure.     

Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice

We tested the hypothesis that chronic treatment with sildenafil attenuates myocardial infarction (MI)-induced heart failure. Sildenafil has potent protective effects against necrosis and apoptosis following ischemia-reperfusion in the intact heart and cardiomyocytes. ICR mice underwent MI by left anterior descending coronary artery ligation and were treated with sildenafil (0.71 mg/kg bid) or saline for 4 wk. Infarct size (IS) was measured 24 h postinfarction, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) were measured by echocardiography. Sildenafil reduced IS (40.0 +/- 4.6%) compared with that in saline (69.6 +/- 4.1%, P < 0.05). NG-nitro-l-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor (15 mg/kg bid), blocked the protective effect of sildenafil (IS, 60.2 +/- 1.6%, P < 0.05 vs. sildenafil). Western blot analysis revealed a significant increase in endothelial NOS/inducible NOS proteins 24 h post-MI after treatment with sildenafil versus saline. Apoptosis decreased from 2.4 +/- 0.3% with saline to 1.2 +/- 0.1% with sildenafil (P < 0.05) on day 7 and from 2.0 +/- 0.2% with saline to 1.2 +/- 0.1% with sildenafil on day 28 (P < 0.05), which was associated with an early increase in the Bcl-2-to-Bax ratio. LVEDD increased from baseline value of 3.6 +/- 0.1 to 5.2 +/- 0.2 and to 5.5 +/- 0.1 mm on days 7 and 28, respectively, with saline (P < 0.05) but was attenuated to 4.4 +/- 0.2 and 4.4 +/- 0.1 mm following sildenafil treatment on days 7 and 28, respectively (P > 0.05 vs. baseline). FS significantly improved post-MI with sildenafil. A marked decline in cardiac hypertrophy was observed with sildenafil, which paralleled a reduction in pulmonary edema. Survival rate was lower with saline (36%) compared with sildenafil (93%, P < 0.05). Sildenafil attenuates ischemic cardiomyopathy in mice by limiting necrosis and apoptosis and by preserving left ventricular function possibly through a nitric oxide-dependent pathway.     

Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart

We tested the hypothesis that left ventricular (LV) remodeling late after myocardial infarction (MI) is associated with myocyte apoptosis in myocardium remote from the infarcted area and is related temporally to LV dilation and contractile dysfunction. One, four, and six months after MI caused by coronary artery ligation, LV volume and contractile function were determined using an isovolumic balloon-in-LV Langendorff technique. Apoptosis and nuclear morphology were determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and Hoechst 33258 staining. Progressive LV dilation 1-6 mo post-MI was associated with reduced peak LV developed pressure (LVDP). In myocardium remote from the infarct, there was increased wall thickness and expression of atrial natriuretic peptide mRNA consistent with reactive hypertrophy. There was a progressive increase in the number of TUNEL-positive myocytes from 1 to 6 mo post-MI (2.9-fold increase at 6 mo; P < 0. 001 vs. sham). Thus LV remodeling late post-MI is associated with increased apoptosis in myocardium remote from the area of ischemic injury. The frequency of apoptosis is related to the severity of LV dysfunction.     

Humoral and hemodynamic responses after left ventricular assist device implantation and heart transplantation

Left ventricular assist device (LVAD) implantation and heart transplantation (HTx) are established therapeutic approaches in the treatment of end-stage heart failure. The postoperative humoral responses to the two treatments have not yet been compared. All patients were treated with inhaled nitric oxide (iNO) on weaning from cardiopulmonary bypass as they presented with pulmonary hypertension. We investigated atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cGMP, endothelin (ET)-1, big endothelin (big ET), and hemodynamic parameters after LVAD implantation (15 patients; age 51 +/- 8 years) or HTx (10 patients; age 53 +/- 6 years) preoperatively, on cardiopulmonary bypass and postoperatively up to 72 hrs after cessation of iNO. Preoperatively, cardiac index (CI), pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and mean atrial pressure (MAP) were similar for both groups. Similarly, ANP, BNP, cGMP, ET-1, and big ET were comparable before surgery. Seventy-two hours after weaning from iNO, the administered epinephrine dose was higher in the HTx group (P = 0.003); whereas the CVP (P = 0.04) and pulmonary vascular resistance (PVR; P = 0.03) were lower. The following humoral parameters differed markedly: ANP (preoperatively: LVAD, 99 +/- 123 pg/ml; HTx, 197 +/- 199 pg/ml; P = 0.14; vs. 72 hrs after iNO: LVAD, 110 +/- 106 pg/ml; HTx, > 640 +/- 0 pg/ml; P = 0.003) and cGMP (preoperatively: LVAD, 4.4 +/- 5.8 pg/ml; HTx, 5.0 +/- 3.0 pg/ml; P = 0.35; vs. 72 hrs after iNO: LVAD, 8.0 +/- 10.8 pg/ml; HTx, 26.2 +/- 15.8 pg/ml; P = 0.02). Although the hemodynamic effects of both LVAD implantation and HTx in the treatment of end-stage heart failure are comparable, except for the effects on CVP and PVR, the humoral responses with respect to ANP and cGMP were strikingly different. These effects are independent of volume status, iNO, and ETs, suggesting a physiologic response to maintain circulatory homeostasis.     

Transesophageal left ventricular posterior wall potential in heart failure patients with biventricular pacing.

INTRODUCTION: Biventricular (BV) pacing is an established therapy for heart failure (HF) patients with intraventricular conduction delay, but not all patients improved clinically. We investigated the interventricular delay (IVD) by means of the transesophageal left ventricular posterior wall potential (LVPWP). MATERIALS AND METHODS, AND RESULTS: A total of 18 HF patients (age 62+/-9 years; 15 males) with NYHA class 3.1+/-0.3, LV ejection fraction 22+/-7%, left bundle branch block and a QRS duration (QRSD) of 171+/-27 ms were analyzed using transesophageal LVPWP before implantation of a BV pacing device. The median follow up was 14+/-14 months. In 14 responders, IVD was 81+/-25 ms with a QRSD/IVD ratio of 2.2+/-0.3 with reclassification of NYHA class 3.1+/-0.3 to 2.0+/-0.5 (p<0.001) and an increase in LV ejection fraction from 22+/-7% to 36+/-11% (p=0.001) during long-term BV pacing. In four non-responders, transesophageal IVD was significantly smaller at 30+/-11 ms (p=0.001). CONCLUSION: Transesophageal IVD may be a useful method to detect responders to BV pacing. Transesophageal LVPWP may be a simple and useful technique to detect clinical responders to BV pacing in HF patients.     

The effect of gender on left ventricular function immediately after the wingate test

The effect of gender on left ventricular systolic function and exercise haemodynamics in healthy young subjects was studied during 30-s all-out sudden strenuous dynamic exercise. A group of 22 men [19.3 (SD 1) years] 20 women [19.1 (SD 1) years] volunteered to participate in this study. Two-dimensional direct M-mode and Doppler echocardiograph studies were performed with the subject in the sitting position. The Doppler examination of flow was located with continuous-wave, interrogating ascending aorta measurements. The subjects completed the study without showing any electrocardiograph abnormalities. An interaction effect with stroke volume (P < 0.05) was characterized by a decrease in the men and an increase of stroke volume in the women. Cardiac output rose significantly (P < 0.05) up to 14.5 (SD 6) l · min⁻¹) for the men and 12.1 (SD 4) l · min⁻¹ for the women compared to the rest values [5.8 (SD 0.4) and 4.7 (SD 0.5) l · min⁻¹, respectively]. Flow velocity integral and acceleration time differed significantly between the two groups at rest (P < 0.05). During exercise these differences showed an interaction effect (P < 0.05). These results would indicate that normal men and women respond to sudden strenuous exercise by reducing their left ventricular systolic function, with a significantly greater decrease in women (P < 0.05). The gender differences in the haemodynamic responses during the present study, may, as suggested by others, be attributable to differences in energy metabolism. In addition, changes in Doppler parameters of aortic flow, haemodynamics and blood pressure responses during sudden strenuous exercise differed markedly from those seen before with endurance exercise. Accepted: 8 January 1997     

Radionuclide left ventricular angiography during exercise in ischemic heart disease.

Radionuclide angiocardiography during exercise is one of the latest advances in nuclear cardiology and is being introduced into clinical practice. In this article the pathophysiological principles of this technique and the method with which it is used to evaluate patients with ischemic heart diseases are outlined, the various patterns of response in these patients are illustrated, and factors that limit the interpretation of the results, including the level of exercise achieved, are discussed.     

Evaluation of global left ventricular function assessment of non-fluorescent electromechanical endocardial mapping compared with biplane left ventricular contrast angiography

Background. Little is known about the diagnostic accuracy of global LV function assessment by electromechanical endocardial mapping (EEM). The aim of the present study was to determine the relationship between global left ventricular (LV) function measured by EEM and biplane left ventricular contrast angiography (LVA) after ST-elevation myocardial infarction (STEMI). Methods. Thirty-seven patients underwent LVA and EEM during routine coronary angiography four months after primary percutaneous intervention for STEMI. Global LV function parameters were available from both techniques in all patients. LVA was regarded as reference standard. Results. All procedures were carried out without adverse events. Average age was 55±10 years and 84% were male. EEM showed an overestimation of end-diastolic volume (EDV) and end-systolic volume (ESV) of 6.5 ml and 25.5 ml, respectively. Correlation (r) was 0.84 (p<0.001) for EDV and 0.74 (p<0.001) for ESV. Average left ventricular ejection fraction (LVEF) measured by EEM was 17.2% point (±11.3% point) lower compared with LVA (r=0.69, p<0.001). Conclusion. Although global functional parameters by EEM correlated well with LVA, the relatively large differences in terms of absolute values for ventricular volumes and LVEF render the two techniques non-interchangeable for global LV-function-data. (Neth Heart J 2010;18:72–77.)     

Echocardiographic AV-interval optimization in patients with reduced left ventricular function

Background

Power Doppler (PD) has improved diagnostic capabilities of vascular sonography, mainly because it is independent from the angle of insonation. We evaluated this technique in a prospective comparison with conventional imaging, consisting in Duplex and Color Doppler, for the evaluation of Renal Artery (RA) stenosis.

Methods

Sensitivity, specificity and predictive values of PD and conventional imaging were assessed in a blinded fashion on eighteen patients, 9 with angiographic evidence of unilateral RA stenosis (hypertensive patients) and 9 with angiographically normal arteries (control group). PD images were interpreted with an angiography-like criteria.

Results

In the control group both techniques allowed correct visualization of 16 out of the 18 normal arteries (93% specificity). Only in five hypertensive patients RA stenosis was correctly identified with conventional technique (56% sensitivity and 86% negative predictive value); PD was successful in all hypertensive patients (100% sensitivity and negative predictive value), since the operators could obtain in each case of RA stenosis a sharp color signal of the whole vessel with a clear "minus" at the point of narrowing of the lumen. All results were statistically significant (p < 0.01).

Conclusions

This study demonstrates that PD is superior to conventional imaging, in terms of sensitivity and specificity, for the diagnosis of RA stenosis, because it allows a clear visualization of the whole stenotic vascular lumen. Especially if it is used in concert with the other sonographic techniques, PD can enable a more accurate imaging of renovascular disease with results that seem comparable to selective angiography.     

False left ventricular aneurysm as a complication of open heart surgery.

A false aneurysm developed at the site of left ventricular venting in an 8-year-old boy who had undergone aortic valve commissurotomy under cardiopulmonary bypass. The diagnosis was made by clinical examination and chest radiography and confirmed by left ventricular cineangiography. The aneurysm was successfully resected.